Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations (IRDs-OSR)

Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations, Monocentric Retrospective Observational Study

Inherited Retinal Diseases (IRDs) are a heterogeneous group of genetically based degenerative retinal disorders, representing a major cause of visual impairment and blindness in working-age adults. Despite the approval of the first gene therapy for RPE65-related IRD (voretigene neparvovec) in 2017, most IRDs remain untreatable, though many gene therapies are in development. Effective trial design and therapy development require a deep understanding of disease natural history and genotype-phenotype correlations. Over 270 IRD-associated genes are known (e.g., ABCA4, USH2A, RPGR, PRPH2, BEST1), each linked to distinct phenotypes and clinical progression. This retrospective study analyzes clinical, functional, and imaging data (Optical Coherence Tomography, Fundus Autofluorescence, Microperimetry) from a large, genetically characterized IRD cohort at the IRCCS Ospedale San Raffaele up to December 31, 2025. The aims are to describe natural history, define genotype-phenotype relationships, and identify structural and functional outcome measures useful for future clinical trial endpoints, supporting personalized prognosis and trial design.

Study Overview

• Status: Not yet recruiting
• Conditions: Stargardt Disease; Retinitis Pigmentosa (RP); Retinal Degenerations
• Intervention / Treatment: Other: No Intervention: Observational Cohort

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Maurizio Battaglia Parodi, MD; Phone Number: 00390226433545; Email: battagliaparodi.maurizio@hsr.it
• Study Contact Backup: Name: Lorenzo Bianco, MD; Phone Number: MD 0039 0226433545; Email: bianco.lorenzo@hsr.it

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Irccs Ospedale San Raffaele
      • Contact: Adelaide Pina; Phone Number: +390226433545; Email: pina.adelaide@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients affected by IRDs genetically confirmed

Description

Inclusion Criteria:

1. Participant completed at least one ophthalmological and retinal imaging examination at our center.
2. Clinically diagnosed with IRD, as per familiy history, clinical signs or symptoms, retinal imaging findings.
3. Definitive genetic diagnosis of IRD with adequate molecular test

Exclusion Criteria:

1. Affected by other retinal or optic nerve conditions potentially affecting analyses (diabetic retinopathy, glaucoma).
2. History of retinotoxic medications (i.e., hydroxychloroquine, pentosan polysulfate sodium, tamoxifen, ritonavir, didanosine, MEK inhibitors) intake.
3. Unclear genetic diagnosis.
4. Incomplete or inadequate ophthalmological and imaging tests.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best-corrected Visual Acuity	Measured on measured Early Treatment Diabetic Retinopathy Study (ETDRS) charts and recorded in logMAR units	through study completion, an average of 1 year
Macular threshold sensitivity	Measured in decibels using fundus- tracked MP (e.g., MAIA device) across a standard grid of 68 central loci under standardized mesopic conditions. Sensitivity deviation from age-matched normative values will also be computed	through study completion, an average of 1 year
Total Macular volume	Measured in mm3 on OCT scans	through study completion, an average of 1 year
Centra Subfield Thickness	Measured in micron on OCT scans	through study completion, an average of 1 year
Preserved Ellipsoid zone area	Measured in mm2 on OCT scans	through study completion, an average of 1 year
Foveal Outer Nuclear Layer thickness	Measured in microns on OCT scans	through study completion, an average of 1 year
Ellipsoid zone loss area	Measured in mm2 on OCT scans	through study completion, an average of 1 year
Hyperautofluorescent (Robson- Holder) ring area	Measured in mm2 on FAF images	through study completion, an average of 1 year
Dereased Autofluorescence area	Measured in mm2 on Fundus autofluorescence images	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Macular Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Stargardt Disease; Retinitis Pigmentosa; Retinal Degeneration
• Other Study ID Numbers: IRDs-OSR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: single center study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No